With the development of modern mass spectrometers (MS) coupled to highly efficient liquid chromatography (LC) systems, it is now possible to measure thousands of metabolites, mainly lipids, in as little as

a few minutes per sample. LC/MS is particularly well-suited to identify novel NAFLD biomarkers, where lipid metabolic changes and the hypoxia-inducible factor cancer lipotoxicity they generate are thought to play a key function in disease development and progression. Recent awareness that each category of lipid consists of thousands of molecular species emphasizes the need to search for individual lipid molecules in addition to measuring total changes in the concentration of fatty acids, glycerophospholipids, diacylglycerols, TAG, and bile acids. Our group has recently shown the potential of such an approach in describing common serum metabolic alterations observed in a gene knockout animal NAFLD model and a small cohort of morbidly obese patients with NAFLD, who are closely matched in clinical features such as sex, age, and BMI.12 Others have used JQ1 datasheet similar techniques to describe a series

of metabolite biomarkers found in the serum and liver tissue of patients with NAFLD who have a variety of clinocopathological characteristics.13 More recently, we studied the serum lipidomics and amino acid profile, as a function of BMI, in about 500 biopsied individuals with normal liver, or who had been diagnosed with steatosis or NASH. This study has identified a BMI-dependent metabolic signature able to reliably distinguish NASH from steatosis, showing an AUROC of 0.85 (Barr J, Lu SC, Mato JM, unpublished data). This list of novel BMI-dependent biomarkers is made Protein kinase N1 of individual molecular species belonging to different lipid categories (i.e., eicosanoids, nonesterified fatty acids,

glycerophospholipids, sphingomyelins, ceramides, diacylglycerols, and TAG). The goal of this metabolomics-based approach is to develop perfect (99%-100% sensitivity and specificity) noninvasive diagnostic tests for liver steatosis, NASH, and fibrosis by combining the tried and trusted old biomarkers with these new lipid biomarkers. These tests should also be responsive to changes in NAFLD severity due to therapeutic intervention and time. This task is not suited for every laboratory, because extreme care needs to be taken to ensure that the analytical methods used are well validated and the new specific biomarkers correctly identified.

[50] Especially, M2 macrophages might negatively regulate liver fibrosis via the production of anti-inflammatory cytokine IL-10.[51] However, under certain conditions, M2 macrophages may also promote liver fibrosis via TGF-β- and MCP-1/CCR2-dependent manners.[50] Although, click here macrophages

can be classified into M1 and M2, there are no significant differences in their morphologic characteristics. Other macrophages such as scar-associated macrophages and BM-derived macrophages have shown to suppress liver fibrosis via matrix metalloproteinase (MMP) productions.[42, 52] Generally, DCs play important roles in both innate and adaptive immune responses as professional antigen-presenting cells.[9] However, the roles of DCs in liver fibrosis are not clearly demonstrated yet. Recent studies show dual roles of liver DCs in liver fibrosis. In thioacetamide-induced liver fibrosis, the characteristics of liver DCs are transformed from tolerogenic to immunogenic, which subsequently enhance inflammatory changes (enhanced activities of NK cells and CD8+ T cells but reduced population of Tregs) in liver fibrosis via the production of TGF-beta inhibitor TNF-α.[53] In contrast, after cessation of liver injury, liver DCs are implicated in the regression

of CCl4-induced liver fibrosis via the production of MMP-9.[54] Therefore, further detailed studies are required to clarify the roles of DC during liver fibrogenesis and regression. HSCs are involved in the pathogenesis of all stages of alcoholic liver disease such as alcoholic steatosis (fatty liver), steatohepatitis, fibrosis, cirrhosis, 4��8C and hepatocellular carcinoma by producing endocannabinoids, proinflammatory cytokines and chemokines, collagen fibers, and retinol metabolites.[55-57] Besides alcohol-mediated activation of HSCs, diverse liver immune cells such as

NK cells, Kupffer cells/macrophages, and IL-17-producing cells are under the influence of alcohol, leading to various interactions with HSCs compared with those in normal circumstances. Chronic alcohol consumption suppresses the cytotoxicity of NK cells against activated HSCs,[37] while alcohol-mediated TLR4 activation in Kupffer cells/macrophages induces enhanced activation of HSCs by producing proinflammatory cytokines such as TNF-α,[55] subsequently accelerating liver fibrosis. In addition, alcohol consumption accumulates IL-17-producing cells including neutrophils in the liver, which subsequently enhance activation of HSCs.[17, 18] However, the interactions between HSCs and other types of liver immune cells, especially adaptive immune cells, in alcoholic liver disease are still unclear. Thus, further studies are strongly required to address those matters. During liver injury, activated HSCs participate in various liver diseases via abnormal ECM accumulation and cytokine productions.

Major complications occurred in 7 patients (3.9%,including 2 peritoneal hemorrhage, 1 symptomatic pleural effusion, 1 septicemia, 1 hemopneumothorax, 1 pneumothorax and 1 worsened jaundice ) following cryoablation and in 6 patients (3.3%, including 2 septicemia, 1 peritoneal hemorrhage, 1 symptomatic pleural effusion, 1 intrahepatic abscess and 1 worsened ascites ) following RFA (P = 0.776). Conclusions: Our

data demonstrated the cryoablation resulted in a significantly lower HCC recurrent rate, although Forskolin both cryoablation and RFA were equally safe and effective with similar 5-year survival rates. (This was a registered clinical trial in China, listed at Clinicaltrial.gov, ID number, 20071203T) Key words: Hepatocellular carcinoma; Cryoablation; Radiofrequency ablation Disclosures: Ke-Qin Hu – Grant/Research Support:

BMS, Gilead, Merck, Vertex, Genentech; Speaking and Teaching: BMS, Gilead, Merck, Vertex, Genentech The following people have nothing to disclose: Chunping Wang, Huaming Wang, Wuwei Yang, Kaiwen Hu, Hui Xie, Wenlin Bai, Zheng Dong, Yinying Lu, Zhen Zeng, Min Lou, Hong Wang, Xudong Gao, Xiujuan Chang, Linjing An, Jianhui Qu, Jin Li, Yongping Yang “
“Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and ranks in the top three causes of cancer deaths in the Asia-Pacific (AP) region.1,2 Hepatitis B and C virus (HBV and HCV) infections are the most common causes of HCC worldwide. Due to the high prevalence of HBV in the AP region, 75% of HCC patients are seen in this region. The incidence of compound screening assay HCC has been static over the

years in the AP region; however, it is rising in the western world, Japan and Australia due to an epidemic of HCV infections.1,2 The number of patients with HCC is expected to increase by two times over the next two decades.3 Eighty percent of HCCs develop in patients with liver cirrhosis. The annual incidence of HCC in HBV-related cirrhosis varies from 2% to 6%, while in HCV-related cirrhosis it is 3–5%.4 The majority of HCCs are detected at a late stage with high mortality. Thus, the yearly fatality ratio is close to one indicating almost all patients with HCC die within one year. There have DNA ligase been significant advances in diagnostic and therapeutic modalities for early HCC. During 1980–1990, detection of early HCC and curative treatment was possible in only 5–10% patients, while this number increased to 30–40% in 1990–2010.1 In a Japanese study,5 it has been shown that in the last three decades there has been an increasing incidence of early stage HCCs, which has led to the potentially curative treatment of these patients. Clinic-based studies from Italy have also shown that there is a decreasing trend in mortality in liver cirrhosis patients with HCC in the last three decades.6 Looking at these data it seems reasonable to have a surveillance program for early detection of HCC.

However, the effect of profibrotic signaling on IFN signaling is not known. Here, the effect of transforming growth factor (TGF)-β signaling on IFN signaling and hepatitis C virus (HCV) replication was examined in Huh-7.5 cells by evaluating the expression of forkhead box O3A (Foxo3a), suppressor of cytokine signaling 3 (Socs3), c-Jun, activating transcription factor 2, ras homolog enriched in brain, and mTORC1. The findings were confirmed in liver tissue samples obtained from 91 patients who received pegylated-IFN and ribavirin combination therapy. TGF-β signaling was significantly up-regulated in the

advanced fibrosis stage of CH-C. A significant positive correlation was observed between the expression of TGF-β2 and mothers against decapentaplegic homolog 2 (Smad2), Smad2 and Foxo3a, and Foxo3a and Socs3 in the liver of CH-C patients. In Huh-7.5 cells, TGF-β1 activated the Foxo3a promoter click here through an AP1 binding site; the transcription factor c-Jun was involved in this activation. Foxo3a activated the Socs3 promoter and increased HCV replication. TGF-β1 also inhibited mTORC1 and IFN signaling. Interestingly, c-Jun and TGF-β signaling was up-regulated in treatment-resistant IL28B minor genotype patients (TG/GG at rs8099917), especially in the early fibrosis stage. Branched chain amino acids or a TGF-β receptor inhibitor canceled these effects and showed an additive effect on the anti-HCV

activity of direct-acting this website antiviral drugs (DAAs). Conclusion: Blocking TGF-β signaling could potentiate the antiviral efficacy of IFN- and/ or DAA-based treatment regimens and would be useful for the treatment of difficult-to-cure CH-C patients. (Hepatology 2014;60:1519–1530) “
“This year marks 80 years since Cuthbert Dukes described a system of staging for rectal cancer.1 His landmark 1958 paper documents outcomes, according to stage, of 2447 cases of rectal adenocarcinoma resected at St Mark’s hospital.2

The paper is remarkable for its clarity, detail and an extraordinary 98.9% follow up. Survival was not dissimilar to that achieved today. Dukes clearly demonstrated that outcome was strongly related to depth of tumor invasion and to the presence of lymph node metastases. Although neither deducible from Dukes’ data, nor anatomically coherent, it was inferred that progression was Fossariinae generally stepwise. Lymph node metastasis was considered to be an intermediate step in a process beginning with invasion through the rectal wall and culminating in distant metastasis. Pathology had thus provided a rational basis for treatment. Early stage disease, as defined by lack of invasion through the muscularis propria, could be considered treatable by local means. Radical surgery was required for more advanced disease and, perhaps, the more radical the better. The technique of the “High Tie” was developed in support of this concept.3 In practice, application of these principles was limited.

Sufficient and consistent supply of CFCs and appropriate financing of haemophilia care will

allow the clinical benefits of more aggressive treatment regimens such as prophylaxis to be realized [44]. Unconstrained demand assumes unlimited supply or availability of CFCs. It is important for manufactures to understand demand to adequately plan production and for national health care policy makers to better allocate financial and other resources [44]. Current treatment paradigms are often dictated by the scarcity of treatment products. Treatment levels have been minimized in many environments because of the cost of CFCs. In the era before recombinant CFCs supply levels were constrained due to the availability of plasma and thus there would have been buy BMN 673 inadequate supplies to sustain higher trough Selleck KU 57788 levels prophylactically. Today,

conceptually, recombinant technology and new advanced therapies on the horizon eliminate the supply constraint. The remaining obstacle is affordability. Patients, governments and industry need to work together to change the paradigm. The new paradigm needs to include the consideration that much more product is needed globally, and that if it were to be made available demand would go up as more and more patients were treated. Thus, rather than managing scarcity, industry would be faced with an expanding market and increased global demand leading to benefits for manufactures, patients and payers alike. Accelerating innovation of treatment products should, in parallel, accelerate global access to Treatment for All. Given a growing global demand for treatment products, present day global economic constraints, and the competitive market pressures that are coming with the arrival of biosimilars and other new therapies (longer half-life therapies

and gene transfer), a newer 21st century business model will be required. Alternative models see more based on high-volume, low margins should be considered. Industry must continue to evolve their business development, marketing and pricing strategies to adapt to a changing and new global reality. Likewise, it is reasonable for payers to expect that continuing optimization and efficiencies achieved in the manufacturing process over the life cycle of a product would be passed on in final product pricing. For some, in the foreseeable future, the definition of optimal treatment may vary based on the economic capacity of a country, or be only incrementally achievable over time. Although, the emerging therapies will afford the opportunity to revisit the current treatment paradigm from purely an economic perspective, no one should lose sight that the overriding goal is to improve care and health outcomes.

This study aimed to evaluate the gastroprotective effect of an ethanolic extract of C. olitorius against ethanol-induced gastric ulcers in adult Sprague Dawley rats. The rats were divided

into seven groups according to their pretreatment: an untreated control group, an ulcer control group, a reference control group (20 mg/kg selleck compound omeprazole), and four experimental groups (50, 100, 200, or 400 mg/kg of extract). Carboxymethyl cellulose was the vehicle for the agents. Prior to the induction of gastric ulcers with absolute ethanol, the rats in each group were pretreated orally. An hour later, the rats were sacrificed, and gastric tissues were collected to evaluate the ulcers and to measure enzymatic activity. The tissues were subjected to histological and immunohistochemical

evaluations. Compared with the extensive mucosal damage in the ulcer control group, gross evaluation revealed a marked protection of the gastric mucosa in the experimental groups, with significantly preserved gastric wall mucus. In these groups, superoxide dismutase and malondialdehyde levels were significantly increased (P < 0.05) and reduced (P < 0.05), respectively. In addition to the histologic analyses (HE and periodic acid-Schiff staining), immunohistochemistry confirmed the protection see more through the upregulation of Hsp70 and the downregulation of Bax proteins. The gastroprotection of the experimental groups was comparable to that of the reference control medicine omeprazole. Our study reports the gastroprotective property of an ethanolic extract of C. olitorius against ethanol-induced gastric mucosal hemorrhagic lesions in rats. “
“Liver cirrhosis is often accompanied by zinc deficiency. The exact mechanisms underlying zinc deficiency remain unclear. This study was undertaken to clarify the influence of diuretics on blood zinc levels and zinc excretion in urine

in liver cirrhosis. Seventy-nine outpatients with liver cirrhosis were divided into four groups: (i) patients receiving Doxorubicin datasheet no zinc preparations or diuretics (LC group); (ii) those receiving zinc preparations only (LCZ group); (iii) those receiving diuretics only (LCD group); and (iv) those receiving both zinc preparations and diuretics (LCDZ group). Among these groups, the effects of the administrated drugs on blood zinc levels and urinary zinc excretion were analyzed. Blood zinc levels were significantly lower in the LCD group (47.8 ± 10.5 μg/dL) than in the other groups (LC: 68.8 ± 17.1 μg/dL, P = 0.0056, post-hoc test; LCZ: 78.4 ± 18.1, P < 0.0001; LCDZ: 70.3 ± 21.4, P = 0.0008). The creatinine-adjusted urinary zinc excretion was significantly higher in the LCDZ group (548.1 ± 407.6 μg/mg creatinine) than in the other groups (LC, 58.5 ± 43.7; LCZ, 208.1 ± 227.8; LCD, 105.2 ± 154.4; each P < 0.0001). The fraction of urinary zinc excretion was also significantly higher in the LCDZ group (5.6 ± 2.9%) than in the other groups (LC, 0.6 ± 0.5; LCD, 1.7 ± 1.5; LCZ, 1.6 ± 1.2; each P < 0.0001).

For construction of pcDNA-MICA-mut or pMyc-MICA-mut, Val348 and Leu349 were substituted for alanine. pcDNA-MICA-del or pMyc-MICA-del, which expresses MICA (or myc-tagged MICA) truncated at Val348, was generated by introducing a stop codon after Gln347. check details The stop codon was inserted after Pro298, the

C-terminus of the putative α3 domain, to construct soluble MICA expression vectors, pcDNA-MICA-sol or pMyc-MICA-sol. Cells were transfected with the MICA expression vectors using Lipofectamine LTX reagent (Invitrogen). As a control, cells were cotransfected with pEGFP-C1 (Clontech, Mountain View, CA) to monitor the transfection efficiencies. The lysates of cells or tissues were prepared as previously described.20 Immunoprecipitation with anti-c-Myc beads was performed for 1 hour at 4°C. Immunocomplexes

were eluted by c-Myc tagged peptide solution (MBL, Woburn, MA). The samples after immunoprecipitation were treated with 250 mU of N-glycosidase F (Roche, Mannheim, Germany) for 3 hours at 37°C. The total cellular protein was electrophoretically separated by sodium dodecyl sulfate-12% polyacrylamide gels and transferred buy AZD1152-HQPA onto polyvinylidene fluoride membrane. The membrane was blocked in Tris-buffered saline-Tween containing 5% skim milk for 1 hour, and then probed with anti-Myc mouse monoclonal antibody (mAb) (Cell Signaling Technology, Danvers, MA), anti-ADAM9 mAb (R&D Systems) at 4°C overnight. Horseradish peroxidase–conjugated anti-rabbit Ab and SuperSignal West Pico System (Pierce, Rockford, IL) were used for the detection of blots. Human HCC tissues (n = 11) obtained at surgical resection were used. Informed consent, under Selleck Cetuximab a protocol approved by Institutional Review Board, was obtained from all

patients before sample acquisition. Liver sections were subjected to immunohistochemical staining using the ABC procedure (Vector Laboratories, Burlingame, CA). The primary Ab used was anti-ADAM9 (R&D Systems). To confirm the specificity of the staining, primary antibodies were incubated with recombinant ADAM9 protein (R&D Systems) for 3 hours and then applied onto liver sections in parallel with staining of the primary Abs as the absorption test. NK cells were isolated from human peripheral blood mononuclear cells by magnetic cell sorting using CD56 MicroBeads according to the manufacturer’s instructions (Miltenyi Biotec, Auburn, CA). The cytolytic abilities of NK cells against ADAM9KD/control HCC cells or 0.5 or 1 μmol/L sorafenib-treated HCC cells were assessed by 4-hour 51Cr-releasing assay with or without MICA/B-blocking Ab (6D4; a generous gift from Dr. Veronika Groh and Dr. Thomas Spies, of the Fred Hutchinson Cancer Research Center, Seattle, WA),7 which binds to the α1 and α2 domains of MICA. All values were expressed as the mean and standard deviation.

The mean pre-program Body Mass Index (BMI) was comparable, 42.5 kg/m2 and 43.5 kg/m2 for the two programs. Mean Excess Weight Loss (%EWL) achieved in the three week program was 17.3% (7.0 kg) and for the extended, 6–12 week program 24.4% (9.2 kg). Twenty-four patients (10.3%) failed

to achieve the program goal of at least 10% EWL and eleven patients (4.7%) withdrew from the program. No adverse events were reported. 98.1% of patients (n = 104) rated the program as valuable and 95.2% rated the VLED AZD1208 price meal replacement product as good or excellent. Conclusions: These data demonstrate that patients can achieve a significant, rapid weight loss in a safe, structured, supervised protocol. Pre-operative weight loss has the potential to reduce the technical difficulty of surgery in the obese patient population, thus improving patient outcomes. The benefit of rapid weight loss for medical conditions requires further research. Further study is required to assess the impact of rapid pre-operative weight loss on surgical outcomes: operation duration, hospital stay, recovery time and post-operative complications. CO MUSUMBA, JC HSU, G AHLENSTIEL, NJ TUTTICCI, KS NANDA, D VAN DER POORTEN, EY LEE, VP KWAN Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, Australia Introduction: Percutaneous endoscopic gastrostomy (PEG) tubes are commonly placed in patients with head and neck cancer (HNC) at risk of malnutrition.

However, PEG placement www.selleckchem.com/products/bmn-673.html in HNC patients using the ‘pull’ technique is complicated by macroscopic and microscopic cutaneous peristomal metastases in 0.5–3% and 9.4%, respectively, leading to a dismal prognosis. We evaluated the feasibility and safety of overtube-assisted

PEG tube placement Tacrolimus (FK506) in patients with HNC as a method of preventing cutaneous metastasis. Materials and Methods: Retrospective analysis of consecutive patients with HNC who underwent PEG placement between June 2011 and December 2013 at Westmead Hospital. All patients received intravenous prophylactic antibiotics using a 3rd generation cephalosporin prior to PEG placement. Under conscious sedation, a 25 cm long esophageal overtube (Guardus®, US. Endoscopy, Mentor, OH) was endoscopically inserted before placement of a 20Fr PEG tube (Bard Access Systems, Salt Lake City, Utah) using the ‘pull’ technique. Following placement, patients were regularly followed up by the nutritional support team and by the oncology team. Main outcome measures were technical success, adverse events and development of overt cutaneous peristomal metastases. Results: 53 patients with HNC underwent overtube-assisted PEG placement overall, 89% prophylactically before commencing curative chemoradiotherapy, and 11% reactively due to treatment of tumor related dysphagia or weight loss. 39 (74%) of the patients were male, with a median age of 59 years (range 32–80). Location of the primary tumor was distributed as follows: 28.3% nasopharynx; 20.8% tongue; 18.9% tonsillar; 5.

6d–f). In addition, significantly increased integrin expression was also detected under subconfluent culture conditions (Fig. 6d–f). IN THE PRESENT study, little or no expression of the β6, β4 and α3 integrins was immunohistochemically shown in CoCC, whereas high expression levels of these integrins were evident in CCC. Integrin mRNA levels were high in most of the CCC cell lines, but they were almost undetectable in most LEE011 supplier of the HCC cell lines, as previously reported for integrin β6.[21] These

results indicated that the expression levels of these integrins, including both the injury-induced type integrin β6 and bile duct-specific integrins β4 and α3 are downregulated in CoCC in contrast to their overexpression in CCC. Furthermore, immunostaining for integrins, Doxorubicin molecular weight particularly integrin β4, revealed high specificity and a highly positive predictive value with regard to differentiation between CoCC and CCC, indicating a diagnostic value of the present immunohistochemical findings. An algorithm for the differential diagnosis of CoCC, CCC and HCC using immunohistochemistry is shown in Figure 7. The high integrin expression frequently encountered in CCC was not related to the gross type and histological differentiation grade of the tumor, even though the peripheral mass-forming type of CCC has been shown to have histological features similar to CoCC.

The aberrant expression of the β6 and β4 integrins, with three different expression patterns, cytoplasmic, cell membrane

Y-27632 2HCl and basal lamina types, in CCC was also demonstrated in the present study, though its significance remains to be clarified. The expression of these integrins in CoCC resembled the expression of integrins in HCC. In addition, the CoCC samples in the present study were significantly associated with chronic viral hepatitis and liver cirrhosis, which is well known in HCC. CoCC exhibits a biliary phenotype with CK7 and CK19 positivity, as does CCC, in addition to a microtubular structure resembling cholangioles or canals of Hering, but it also has been shown to have some intermediate features with a trabecular structure and AFP positivity similar to HCC. In addition, CoCC has been reported to show hepatic stem cell/progenitor cell features that are suggestive of hepatic progenitor cell origin.[4, 30, 31] The low expression of integrins in CoCC, similar to that in HCC in the present study, may be associated with intermediate phenotypes of CoCC cells that are possibly derived from hepatic progenitor cells. In fact, the downregulation of integrin expression in CoCC components and HCC components in contrast to the enhanced expression in CCC components was also observed in classical CHC, the histogenesis of which has been suggested to be associated with hepatic progenitor cells.

6d–f). In addition, significantly increased integrin expression was also detected under subconfluent culture conditions (Fig. 6d–f). IN THE PRESENT study, little or no expression of the β6, β4 and α3 integrins was immunohistochemically shown in CoCC, whereas high expression levels of these integrins were evident in CCC. Integrin mRNA levels were high in most of the CCC cell lines, but they were almost undetectable in most BGB324 of the HCC cell lines, as previously reported for integrin β6.[21] These

results indicated that the expression levels of these integrins, including both the injury-induced type integrin β6 and bile duct-specific integrins β4 and α3 are downregulated in CoCC in contrast to their overexpression in CCC. Furthermore, immunostaining for integrins, Poziotinib particularly integrin β4, revealed high specificity and a highly positive predictive value with regard to differentiation between CoCC and CCC, indicating a diagnostic value of the present immunohistochemical findings. An algorithm for the differential diagnosis of CoCC, CCC and HCC using immunohistochemistry is shown in Figure 7. The high integrin expression frequently encountered in CCC was not related to the gross type and histological differentiation grade of the tumor, even though the peripheral mass-forming type of CCC has been shown to have histological features similar to CoCC.

The aberrant expression of the β6 and β4 integrins, with three different expression patterns, cytoplasmic, cell membrane

Branched chain aminotransferase and basal lamina types, in CCC was also demonstrated in the present study, though its significance remains to be clarified. The expression of these integrins in CoCC resembled the expression of integrins in HCC. In addition, the CoCC samples in the present study were significantly associated with chronic viral hepatitis and liver cirrhosis, which is well known in HCC. CoCC exhibits a biliary phenotype with CK7 and CK19 positivity, as does CCC, in addition to a microtubular structure resembling cholangioles or canals of Hering, but it also has been shown to have some intermediate features with a trabecular structure and AFP positivity similar to HCC. In addition, CoCC has been reported to show hepatic stem cell/progenitor cell features that are suggestive of hepatic progenitor cell origin.[4, 30, 31] The low expression of integrins in CoCC, similar to that in HCC in the present study, may be associated with intermediate phenotypes of CoCC cells that are possibly derived from hepatic progenitor cells. In fact, the downregulation of integrin expression in CoCC components and HCC components in contrast to the enhanced expression in CCC components was also observed in classical CHC, the histogenesis of which has been suggested to be associated with hepatic progenitor cells.